Radiant energy – Ionic separation or analysis – With sample supply means
Reexamination Certificate
2001-03-02
2004-03-30
Wells, Nikita (Department: 2881)
Radiant energy
Ionic separation or analysis
With sample supply means
C250S281000, C250S282000, C250S292000
Reexamination Certificate
active
06713757
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to controlling the temporal response of mass spectrometers, and particularly to detecting ions of interest by mass spectrometry, wherein ions are processed through a section of a mass spectrometer that operates under conditions enabling ion-neutral collisions. More particularly, this invention is concerned with a technique to enable an existing charge distribution in such a processing section to be flushed out rapidly and then quickly reestablished, so as to give, at an output, a reproducible and quickly repeatable ion current, thereby to give better control of the temporal response.
BACKGROUND OF THE INVENTION
In mass spectrometry, a reaction and/or collision cell is often employed (to remove an isobaric interference through reaction or fragmentation with a reaction/collision gas, or shift the ion of interest to another mass by reacting with a reaction gas, or fragment the ion of interest and collect the fragment ions for subsequent mass analysis). Collision or reaction cells have the problem that, due to the high pressure necessary present within them, flow of ions can be slowed. In a variety of standard mass spectrometer operating regimes, this can cause difficulties, since it is often required to switch, rapidly, between different top operating states. However, for collision cells, when the operating state is changed, it can take some time for an output ion stream to stabilize, due to the slow ion motion through the collision cells and space charge effects within the collision cell. There are also other sections of standard mass spectrometer systems which can also slow motion of ions and show slow response times to changes in operating conditions. For example, some mass spectrometers can have mass analysis sections that operate at relatively high pressures, and, in many mass spectrometer systems, it is common to have an input section with a focusing multipole device interposed between an atmospheric pressure source and the high vacuum sections of the mass spectrometer, the input section operating at some intermediate pressure. Thus, all these sections pose problems for an operating scheme where the operating state is required to change rapidly.
It is also to be recognized that, in the field of mass spectrometry, there are large numbers of different mass spectrometers. For many purposes, these can be broken down into two broad categories. In one category, mass spectrometers are configured to analyze inorganic analytes. One common technique is inductively coupled plasma mass spectrometry (ICP-MS). An inductively coupled plasma source has, for example, an argon gas that is excited by inductive heating, to generate a plasma. The analyte is then injected into the plasma, where it is ionized. While this does effectively ionize the analyte, the resultant ion stream into the mass spectrometer provides a very large ion current, including a significant proportion of argon ions or other ions derived from the sample. This can lead to significant space charge effects within a collision/reaction cell.
The second significant category of mass spectrometers is that intended for analyzing organic compounds or analytes. Organic compounds commonly have large, complex structures, and must be ionized with some care, to avoid unwanted degradation or premature fragmentation of the analytes. Common ionization techniques include electrospray, nanospray and the like. Other ionization sources include glow discharge, microwave induced plasma, (both of these are also quite common in inorganic mass spectrometry) corona discharge, etc. It is becoming common practice, for analysis of organic compounds, to provide complex reaction schemes, where analytes are fragmented by collision or reaction, and a particular fragment is selected and then subject to a subsequent stage of collision or reaction. Systems have been proposed that would enable any desired number of steps of fragmentation and ion selection to be affected. It will also be understood that, within any mass spectrometer system, a variety of different reaction/collision cells (e.g. high order multipoles, ring guides and the like) can be used, and similarly that a variety of mass analysis sections can be employed (e.g. time of flight, magnetic sectors, ions traps, etc.).
Some of the inventors of the present application had previously developed an improvement to the basic ICP-MS system that provides for applying a pass band, to the collision cell. This mass spectrometer system is now identified as a Dynamic Reaction Cell (DRC) and is marketed by the assignee of the present invention. This essentially recognizes that while true mass filtering cannot be achieved in the collision cell, it is possible to apply a pass band, so as to reject ions that have m/z ratios substantially different from an ion of interest. This can be used to interrupt sequential chemistry that occurs within the collision cell, which can result in interferences with ions of interest. This Dynamic Reaction Cell is disclosed in U.S. Pat. No. 6,140,638, and like other instruments with collision/reaction cells, there can be problems in the time taken for the reaction cell to reach equilibrium following a change in operating conditions.
As noted, a problem with a collision cell is that when there is any substantial change in the operating condition, e.g. a change in the input ion current or change in fields applied to the cell, this should be reflected in the ion current output from the collision cell, but often it takes some time for the establishment of a new, stable charge distribution within the cell. During this time, an ion stream extracted from the cell can show fluctuations or transients. As ion motion is slowed within the collision/reaction cell, it simply takes time for ions to travel through the collision/reaction cell. Particularly for ICP-MS, the stronger ion current leads to a strong space charge effect, which can also significantly affect the ion density distribution and slow down changing of the ion population to reflect the new operating state. The present inventors have observed prolonged recovery of tho ion population, when the ion density is changed through a wide variety of different inputs. If the degree to which the ion density is changed is variable, the period of recovery is also variable.
It is to be noted that in the case of the DRC, common practice is for the bandpass of the, or the electrical parameters of the, reaction cell to be adjusted in concert with the mass selected by a down stream mass analyzer. Capacitive coupling between the collision/reaction cell and the mass analyzer can be provided but generally this does not provide the required bandpass. When a large jump in mass is executed, with the band pass of the DRC concomitantly adjusted, this can result in dominant ions previously included in the band pass being excluded, or vice versa. Typically, following a large jump in mass, the ion signal from the collision/reaction cell is initially suppressed and increases to a stable level but it is possible that the opposite could occur.
The issue of moving ions through pressurized sections of mass spectrometers, more specifically through collision cells, has been addressed in instruments intended primarily for analyzing organic analytes. Thus, U.S. Pat. No. 5,847,386 (assigned to the assignee of the present invention) discloses a mass spectrometer which provides for an axial field in high pressure sections of a mass spectrometer. These high pressure sections, in the disclosed embodiment, have quadrupole rod sets and a number of techniques are disclosed for applying the axial field to these rod sets. For example, the rods can be specifically shaped or orientated to generate the axial field, or an auxiliary rod set can be provided to generate the axial field, or the rod set can be segmented, to enable segments to be held at different DC potentials.
U.S. Pat. No. 5,847,386 is primarily concerned with a triple quadrupole instrument, in which a collision cell is located between two mass analysis sections. It proposes
Bandura Dmitry R.
Baranov Vladimir I.
Beres Steven A.
Tanner Scott D.
Bereskin & Parr
MDS Inc.
Wells Nikita
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